translational isomerism in some two- and three-station [2]rotaxanes†

Translational Isomerism in Some Two- and Three-Station[2]Rotaxanes†

David B. Amabilino, Peter R. Ashton, Sue E. Boyd, Marcos Gomez-Lopez, Wayne Hayes, andJ. Fraser Stoddart*

School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.

Received July 3, 1996X

The template-directed syntheses of three [2]rotaxanes are described. They all have dumbbellcomponents, with both hydroquinone and resorcinol rings inserted into polyether chains terminatedby tetraarylmethane stoppers, that become encircled during the key self-assembly processes bythe tetracationic cyclophane, cyclobis(paraquat-p-phenylene), with its two π-electron deficientbipyridinium units. It has been demonstrated by low-temperature 1H NMR spectroscopy that theπ-electron deficient tetracationic cyclophane has a remarkably high preference to reside aroundthe hydroquinone ring in these molecular shuttles. This observation illustrates how a very smallconstitutional differenceshydroquinone versus resorcinol recognition sitesscan lead to theoverwhelming preference for one translational isomer over another in this particular range of[2]rotaxanes.

Introduction

Supramolecular chemists1 employ the very same non-covalent bonding interactionsse.g., π-π stacking interac-tions2 and hydrogen bonds3swhich regulate biologicalsystems and processes in order to construct a series offascinating unnatural interlocked molecular compounds,4such as the catenanes and rotaxanes.5 In recent times,

the supramolecular chemist has adopted concepts suchas self-assembly,6 self-replication,7 and self-organization8

that are prolific in biology and applied them successfullyinto the artificial world of synthetic chemistry. The firstinefficient syntheses9 of catenanes and rotaxanes reliedupon the statistical threading of a linear componentthrough a cyclic one. However, it has been possible todesign and synthesize well-defined compatible and comple-mentary molecular components with the ability to rec-ognize each other and then to self-assemble them spon-taneously into molecular assemblies by employingnoncovalent bonding interactions. Notable examples,which illustrate the potential of the self-assembly strat-egy, have been described by Sauvage and co-workers,10

who have designed and prepared an impressive array ofcatenanes, rotaxanes, and knots using a copper(I)-basedtemplate procedure. Hydrogen bonding has been em-ployed more recently to self-assemble another class ofcatenanes and rotaxanes.11 The ability of macrocyclicpolyethers to form pseudorotaxane-like inclusion com-

† Molecular Meccano. 17. For Part 16, see: Asakawa, M.; Ashton,P. R.; Boyd, S. E.; Brown, C. L.; Menzer, S.; Pasini, D.; Stoddart, J. F.;Tolley, M. S.; White, A. J. P.; Williams, D. J.; Wyatt, P. G. Chem. Eur.J. 1997, 3, 463-481.

X Abstract published in Advance ACS Abstracts, April 1, 1997.(1) (a) Lehn, J.-M. Angew. Chem., Int. Ed. Engl. 1988, 27, 89-112.

(b) Cram, D. J. Angew. Chem., Int. Ed. Engl. 1988, 27, 1009-1020. (c)Pedersen, C. J. Angew. Chem., Int. Ed. Engl. 1988, 27, 1021-1027.(d) Lehn, J.-M. Supramolecular Chemistry: Concepts and Perspectives,VCH, Weinheim, 1995.

(2) (a) Hunter, C. A.; Sanders, J. K. M. J. Am. Chem. Soc. 1990,112, 5525-5534. (b) Jorgensen, W. L.; Severance, D. L. J. Am. Chem.Soc. 1990, 112, 4768-4774. (c) Hunter, C. A. Angew. Chem., Int. Ed.Engl. 1993, 32, 1584-1586. (d) Cozzi, F.; Cinquini, M.; Annuziata, R.;Dwyer, T.; Siegel, J. S. J. Am. Chem. Soc. 1993, 115, 5330-5331. (e)Cozzi, F.; Ponzoni, F.; Annunziata, R.; Cinquini, M.; Siegel, J. S. Angew.Chem., Int. Ed. Engl. 1995, 34, 1019-1020.

(3) (a) Burley, S. K.; Petsko, G. A. Science 1985, 229, 2-28. (b)Desiraju, G. R. Acc. Chem. Res. 1991, 24, 290-296. (c) Aakeroy, C. B.;Seddon, K. R. Chem. Soc. Rev. 1993, 397-407. (d) Paliwell, S.; Geib,S.; Wilcox, C. S. J. Am. Chem. Soc. 1994, 116, 4497-4498. (e) Nishio,M.; Umezawa, Y.; Hirota, M.; Takeuchi, Y. Tetrahedron 1995, 51,8665-8701. (e) Fan, E. K.; Yang, J.; Geib, S. J.; Stoner, T. C.; Hopkins,M. D.; Hamilton, A. D. J. Chem. Soc., Chem. Commun. 1995, 1251-1252. (f) Endo, K.; Sawati, T.; Koyanagi, M.; Kobayashi, K.; Masuda,H.; Aoyama, Y. J. Am. Chem. Soc. 1995, 117, 8341-8352. (g) Meissner,R. S.; Rebek, J., Jr.; de Mendoza, J. Science 1995, 270, 1485-1488.(h) Bernstein, J.; Davis R. E.; Shimoni, L.; Chang, N.-L. Angew. Chem.,Int. Ed. Engl. 1995, 34, 1555-1573. (i) Desiraju, G. R. Angew. Chem.,Int. Ed. Engl. 1995, 34, 2311-2327. (k) Desiraju, G. R.; Krishnamo-ham-Sharma, C. V. The Crystal as a Supramolecular Entity: JohnWiley & Sons, Ltd: New York, 1996; pp 31-61.

(4) (a) Walba, D. M. Tetrahedron 1985, 41, 3161-3212. (b) Am-abilino, D. B.; Ashton, P. R.; Reder, A. S.; Spencer, N.; Stoddart, J. F.Angew. Chem., Int. Ed. Engl. 1994, 33, 1286-1290. (c) Nierengarten,J.-F.; Dietrich-Buchecker, C. O.; Sauvage, J-P. J. Am. Chem. Soc. 1994,116, 375-376. (d) Armspach, D.; Ashton, P. R.; Ballardini, R.; Balzani,V.; Godi, A.; Moore, C. P.; Prodi, L.; Spencer, N.; Stoddart, J. F.; Tolley,M. S.; Wear, T. J.; Williams, D. J. Chem. Eur. J. 1995, 1, 33-55. (e)Sleiman, H.; Baxter, P.; Lehn, J.-M.; Rissanen, K. J. Chem. Soc., Chem.Commun. 1995, 715-716.

(5) (a) Schill, G. Catenanes, Rotaxanes and Knots: Academic Press:New York, 1971. (b) Chambron, J. C.; Dietrich-Buchecker, C. O.;Nierengarten, J. F.; Sauvage, J.-P. Pure Appl. Chem. 1994, 66, 1543-1550. (c) Gibson, H. W.; Marand, H. Adv. Mater. 1993, 5, 11-21. (d)Gibson, H. W.; Bheda, M. C.; Engen, P. T. Prog. Polym. Sci. 1994, 19,843-945. (e) Amabilino, D. B.; Stoddart, J. F. Chem. Rev. 1995, 95,2725-2828.

(6) (a) Lindsey, J. S. New J. Chem. 1991, 15, 153-180. (b) Mathias,J. P.; Seto, C.; Whitesides, G. M. Science 1991, 254, 1312-1319. (c)Philp, D.; Stoddart, J. F. Synlett 1991, 445-458. (d) Wyler, R.; deMendoza, J.; Rebek, J., Jr. Angew. Chem., Int. Ed. Engl. 1994, 263,1267-1268. (e) Whitesides, G. M.; Simanek, E. E.; Mathias, J. P.; Seto,C. T.; Chin, D. N.; Mammen, M.; Gordon, D. M.; Acc. Chem. Res. 1995,28, 37-44. (d) Lawrance, D. S.; Jiang, T.; Levett, M. Chem. Rev. 1995,95, 2229-2260. (g) Philp, D.; Stoddart, J. F. Angew. Chem., Int. Ed.Engl. 1996, 35, 1154-1196.

(7) (a) Terfort, A.; von Kiedrowski, G.; Sievers, D. Angew. Chem.,Int. Ed. Engl. 1992, 31, 654-656. (b) Sievers, D.; von Kiedrowski, G.Nature (London) 1994, 369, 221-224. (c) Conn, M. M.; Wintner, E.A.; Rebek, J., Jr. Angew. Chem., Int. Ed. Engl. 1994, 33, 1577-1579.(d) Rebek, J., Jr. Sci. Am. 1994, 369, 221-224. (e) Menger, F. M.;Eliseev, A. V.; Khajin, N. A.; Sherrod, M. J. J. Org. Chem. 1995, 60,2870-2878.

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Chem. Soc. 1984, 106, 3043-3045. (b) Dietrich-Buchecker, C. O.;Sauvage, J.-P. Angew. Chem., Int. Ed. Engl. 1989, 28, 189-192. (c)Diederich, F.; Dietrich-Buchecker, C. O.; Nierengarten, J.-F.; Sauvage,J.-P. J. Chem. Soc., Chem. Commun. 1995, 781-782. (d) Wu, C.;Lecavalier, P. R.; Shen, Y. X.; Gibson, H. W. Chem. Mater. 1991, 3,569-572.

3062 J. Org. Chem. 1997, 62, 3062-3075

S0022-3263(96)01258-3 CCC: $14.00 © 1997 American Chemical Society

plexes with linear secondary dialkylammoniun salts12provides supramolecular chemists with further alterna-tive building blocks for the construction of mechanically-interlocked molecular assemblies and supramoleculararrays.13

Rotaxanes, although lacking the topological appeal ofthe catenanes, have been the subject of intense researchbecause of their abacus-like geometry which makes theman obvious initial starting point for the investigation ofswitching phenomena in molecular systems.14 They canalso be incorporated into polymers, i.e., polyrotaxanes,15bringing together the scientific disciplines of supramo-lecular and macromolecular chemistry.Our own research has concentrated on the investiga-

tions of interlocked and intertwined superstructuresformed by the self-assembly of π-electron rich (e.g.,hydroquinone rings) and π-electron deficient (e.g., 4,4′-bipyridinium units) components.16 The molecular rec-ognition that promotes the formation of these catenanesand rotaxanes containing these building blocks remainsintact in the final interlocked molecules and intertwined

supermolecules, making them ideal for studying the roleof constitutional change upon the nature of noncovalentbonding interactions.17

Translational isomerism17 has been observed previ-ously in both catenanes and rotaxanes. In the latter case,a series of desymmetrized molecular shuttles18si.e.,[2]rotaxanes, in which, for example, the π-electron defi-cient tetracationic cyclophane moves between two de-generate π-electron rich stationsshave been designedand synthesized. It has been possible to modify thedumbbell component in such a way that it incorporates

(11) (a) Hunter, C. A. J. Am. Chem. Soc. 1992, 114, 5303-5311. (b)Vogtle, F.; Meier, S.; Hoss, R. Angew. Chem., Int. Ed. Engl. 1992, 31,1619-1621. (c) Carter, F. J.; Hunter, C. A.; Shannon, R. J. J. Chem.Soc., Chem. Commun. 1994, 1277-1280. (d) Vogtle, F.; Handel, M.;Meier, S.; Ottens-Hildebrandt, S.; Ott, F.; Schmidt, T. Liebigs Ann.1995, 739-743. (e) Johnston, A. G.; Leigh, D. A.; Pritchard, R. J.;Deegan, M. D. Angew. Chem., Int. Ed. Engl. 1995, 34, 1212-1216. (f)Johnston, A. G.; Leigh, D. A.; Nezhat, L.; Smart, J. P.; Deegan, M. D.Angew. Chem., Int. Ed. Engl. 1995, 34, 1209-1212. (g) Leigh, D. A.;Moody, K.; Smart, J. P.; Watson, K. J.; Slawin, A. M. Z. Angew. Chem.,Int. Ed. Engl. 1996, 35, 306-310.

(12) (a) Ashton, P. R.; Campbell, P. J.; Chrystal, E. J. T.; Glink, P.T.; Menzer, S.; Philp, D.; Spencer, N.; Stoddart, J. F.; Tasker, P. A.;Williams, D. J. Angew. Chem., Int. Ed. Engl. 1995, 34, 1865-1868.(b) Ashton, P. R.; Chrystal, E. J. T.; Glink, P. T.; Menzer, S.; Schiavo,C.; Stoddart, J. F.; Tasker, P. A.; Williams, D. J. Angew. Chem., Int.Ed. Engl. 1995, 34, 1869-1871. (c) Glink, P. T.; Schiavo, C.; Stoddart,J. F.; Williams, D. J. Chem. Commun. 1996, 1483-1490.

(13) (a) Kolchinsky, A. G.; Busch, D. H.; Alcock, N. W. J. Chem. Soc.,Chem. Commun. 1995, 1289-1291. (b) Ashton, P. R.; Glink, P. T.;Philp, D.; Menzer, S.; Schiavo, C.; Spencer, N.; Stoddart; J. F.; Tasker,P. A.; White, A. J. P.; Williams, D. J. Chem. Eur. J. 1996, 2, 709-728.(c) Ashton, P. R.; Glink, P. T.; Stoddart, J. F.; Tasker, P. A.; White, A.J. P.; Williams, D. J. Chem. Eur. J. 1996, 2, 729-736.

(14) Feynman, R. P. Sat. Rev. 1960, 43, 45-47. (b) Drexler, K. E.Nanosystems: Molecular Machinery, Manufacturing, and Computa-tion: Wiley Interscience: New York, 1992. (c) Bissell, R. A.; de Silva,A. P.; Gunaratne, H. Q. M.; Lynch, P. L. M.; Maguire, G. E. M.;Sandanayake, K. R. A. Chem. Soc. Rev. 1992, 21, 187-195. (d) Feringa,B. L.; Jager, W. F.; de Lange, B. Tetrahedron 1993, 49, 8267-8310.(e) Kelly, T. R.; Bowyer, M. C.; Bhaskar, K. V.; Bebbiongton, D.; Garcıa,A.; Lang, F.; Kim, M. H.; Jette, M. P. J. Am. Chem. Soc. 1994, 116,3657-3658. (f) Kawai, S. H.; Gilat, S. L.; Lehn, J.-M. J. Chem. Soc.,Chem. Commun. 1994, 1011-1013. (g) James, T. D.; Sandanayake,K. R. A.; Shinkai, S. Nature 1995, 374, 345-347. (h) James, T. D.;Shinkai, S. J. Chem. Soc., Chem. Commun. 1995, 1483-1485.

(15) (a) Harada, A.; Li, J.; Kamachi, M. Nature (London) 1992, 356,325-327. (b) Sekido, N.; Mukaida, N.; Harada, A.; Nakanishi, S.;Watanabe, Y.; Matsushimu, K. Nature (London) 1993, 365, 654-657.(c) Harada, A.; Li, J.; Nakamitsu, T.; Kamachi, M. J. Org. Chem. 1993,58, 7524-7528. (d) Harada, A.; Li, J.; Kamachi, M. Chem. Lett. 1993,237-240. (e) Harada, A.; Li, J.; Suzuki, S.; Kamachi, M. Macromol-ecules 1993, 26, 5267-5268. (f) Harada, A.; Li, J.; Kamachi, M.Macromolecules 1993, 26, 5698-5703. (g) Harada, A.; Li, J.; Kamachi,M. Macromolecules 1994, 27, 4538-4543. (h) Harada, A.; Li, J.;Kamachi, M. Nature (London) 1994, 370, 126-128. (i) Wenz, G.; vonder Bey, E.; Schmidt, L. Angew. Chem., Int. Ed. Engl. 1992, 31, 783-785. (j) Wenz, G.; Keller, B. Angew. Chem., Int. Ed. Engl. 1992, 31,197-199. (k) Wenz, G.; Wolf, F.; Wagner, M.; Kubik, S. New J. Chem.1993, 17, 729-738. (l) Wenz, G.; Keller, B. Makromol. Chem., Macro-mol. Symp. 1994, 87, 11-16. (m) Wenz, G. Angew. Chem., Int. Ed.Engl. 1994, 33, 803-821. (n) Marsella, M. J.; Carrol, P. J.; Swager, T.M. J. Am. Chem. Soc. 1994, 116, 9347-9348. (o) Zhou, Q.; Swager, T.M. J. Am. Chem. Soc. 1995, 117, 7017-7018. (p) Amabilino, D. B.;Parsons, I. W.; Stoddart, J. F. Trends Polym. Sci. 1994, 2, 146-152.(q) Gibson, H. W.; Bheda, M. C.; Engen, P.; Shen, Y. X.; Sze, J.; Zhang,H.; Gibson, M. D.; Delaviz, Y.; Lee, S.-H.; Liu, S.; Wang, L.; Nagvekar,D.; Rancourt, J.; Taylor, L. T. J. Org. Chem. 1994, 59, 2186-2196. (r)Gibson, H. W.; Liu, S.; Lecavalier, P.; Wu, C.; Shen, Y. X. J. Am. Chem.Soc. 1995, 117, 852-874.

(16) (a) Ashton, P. R.; Goodnow, T. T.; Kaifer, A. E.; Reddington,M. V.; Slawin, A. M. Z.; Spencer, N.; Stoddart, J. F.; Vicent, C.;Williams, D. J. Angew. Chem., Int. Ed. Engl. 1989, 28, 1369-1399.(b) Anelli, P. L.; Ashton, P. R.; Ballardini, R.; Balzani, V.; Delgado,M.; Gandolfi, M. T.; Goodnow, T. T.; Kaifer, A. E.; Philp, D.; Pietrasz-kiewicz, M.; Prodi, L.; Reddington, M. V.; Slawin, A. M. Z.; Spencer,N.; Stoddart, J. F.; Vicent, C.; Williams, D. J. J. Am. Chem. Soc. 1992,114, 193-218. (c) Amabilino, D. B.; Ashton, P. R.; Brown, C. L.;Cordova, E.; Godınez, L. A.; Goodnow, T. T.; Kaifer, A. E.; Newton, S.P.; Pietraskiewicz, M.; Philp, D.; Raymo, F. M.; Reder, A. S.; Rutland,M. T.; Slawin, A. M. Z.; Spencer, N.; Stoddart, J. F., Williams, D. J. J.Am. Chem. Soc. 1995, 117, 1271-1293.

(17) (a) Ashton, P. R.; Ballardini, R.; Balzani, V.; Gandolfi, M. T.;Blower, M.; Prodi, L.; McLean, C. H.; Philp, D.; Spencer, N.; Stoddart,J. F.; Tolley, M. S. New J. Chem. 1993, 17, 689-695. (b) Ashton, P.R.; Ballardini, R.; Balzani, V.; Gandolfi, M. T.; Marquis, D. J.-F.; Perez-Garcıa, L.; Prodi, L.; Stoddart, J. F.; Venturi, M. J. Chem. Soc., Chem.Commun. 1994, 177-180. (c) Ashton, P. R.; Preece, J. A.; Stoddart, J.F.; Tolley, M. S.; White A. J. P.; Williams, D. J. Synthesis 1994, 1344-1352. (d) Amabilino, D. B.; Ashton, P. R.; Perez-Garcıa, L.; Stoddart,J. F. Angew. Chem., Int. Ed. Engl. 1995, 34, 2378-2380.

(18) Anelli, P. R.; Spencer, N.; Stoddart, J. F. J. Am. Chem. Soc.1991, 113, 5131-5133.

Scheme 1

Translational Isomerism in [2]Rotaxanes J. Org. Chem., Vol. 62, No. 10, 1997 3063

two nondegenerate π-electron rich stations, one of thema hydroquinone ring and the other a p-xylene,19 anindole,20 or a tetrathiafulvalene unit.21 Furthermore, amolecular switch,22 inspired by the translational isomer-ism displayed in these desymmetrized [2]rotaxanes, hasbeen constructed in which one of the π-electron richstations is a benzidine unit and the other one is abiphenol unit. In the case of this particular molecularshuttle, the control of the movement of the tetracationiccyclophane can be effected either chemically or electro-chemically.A [2]catenane, 2‚4PF6, incorporating a resorcinol unit

(1,3-dihydroxybenzene) in the macrocyclic polyether com-ponent, namely, (p-phenylene)(m-phenylene)-33-crown-10 (1), with the tetracationic cyclophane cyclobis(paraquat-p-phenylene) as the π-electron deficient component, has

been self-assembled23 previously in 15% yield (Scheme1). It was observed that changing the constitution of themacrocyclic polyether not only affects drastically theefficiency of the self-assembly process but it also altersthe nature of the dynamic motion of the two interlockedrings with respect to each other. Variable temperature1H NMR spectroscopic studies carried out on a CD3COCD3

solution of 2‚4PF6 revealed the existence (Scheme 2) oftwo translational isomers, A and B.23 The translationalisomer ratio A:B was found to be 98:2 at 253 K. It isnoteworthy that this remarkable preference for the

(19) Ashton, P. R.; Bissell, R. A.; Spencer, N.; Stoddart, J. F.; Tolley,M. S. Synlett 1992, 914-918.

(20) Ashton, P. R.; Bissell, R. A.; Gorski, R.; Philp, D.; Spencer, N.;Stoddart, J. F.; Tolley, M. S. Synlett 1992, 919-922.

(21) Ashton, P. R.; Bissell, R. A.; Spencer, N.; Stoddart, J. F.; Tolley,M. S. Synlett 1992, 923-926.

(22) Bissell, R. A.; Cordova, E.; Kaifer, A. E.; Stoddart, J. F. Nature(London) 1994, 369, 133-137.

(23) (a) Amabilino, D. B.; Ashton, P. R.; Brown, G. R.; Hayes, W.;Stoddart, J. F.; Tolley, M. S.; Williams, D. J. J. Chem. Soc., Chem.Commun. 1994, 2479-2482. (b) Amabilino, D. B.; Anelli, P.-L.; Ashton,P. R.; Brown, G. R.; Cordova, E.; Godınez, L. A.; Hayes, W.; Kaifer, A.E.; Philp, D.; Slawin, A. M. Z.; Spencer, N.; Stoddart, J. F.; Tolley, M.S.; Williams, D. J. J. Am. Chem. Soc. 1995, 117, 11142-11170.

Scheme 2 Scheme 3

3064 J. Org. Chem., Vol. 62, No. 10, 1997 Amabilino et al.

inclusion of the hydroquinone ring within the cavity ofthe tetracationic cyclophane was exhibited for 2‚4PF6savery simple desymmetrized [2]catenane.In this paper, we report on the self-assembly of three

new [2]rotaxanes containing hydroquinone and resorcinolrings in their dumbbell components. We show how 1HNMR spectroscopic studies provide information about the

different translational isomers and how we are able toconclude that the high translational selectivity observedin the [2]catenane 2‚4PF6 does translate into the analo-gous [2]rotaxanes. In addition, the translational selectiv-ity displayed by the three new molecular shuttles givesinformation about the preferential sites of residence ofthe π-electron deficient tetracationic cyclophane, not onlyin relation to the stereoelectronic nature of the π-electronrich stations but also in respect to the symmetries of theπ-electron rich dumbbell components. All of this infor-mation improves our understanding of the nature of thenoncovalent bonding interactions which regulate the self-assembly processes, enabling the future construction offunctioning molecular assemblies and supramoleculararrays.

Results and Discussion

Synthesis. The first objective was to synthesize adesymmetrized dumbbell compound, comprising one re-sorcinol and one hydroquinone ring as the potentialπ-electron rich recognition sites. In order to achieve this

Figure 1. Mass spectrum of the two-station [2]rotaxane23‚4PF6.

Scheme 4

Scheme 5


goal, the synthetic strategy outlined in Scheme 3 wasapplied in the first instance. An excess of resorcinol wasreacted with benzyl bromide, under mildly basic condi-tions, to produce the phenol 3.24 Alkylation of the phenol3 with the tosylate 420 in the presence of base yieldedthe benzyl-protected phenol 5 in good yield. Hydro-genolysis of the O-benzyl groups in the masked phenol5, under standard conditions, afforded the phenol 6 in97% yield.The other half of the dumbbell compound, comprising

the π-electron rich hydroquinone ring, was synthesizedaccording to the route outlined in Schemes 4 and 5.Commercially available 4-(benzyloxy)phenol (7) was alky-lated with 2-(2-(2-chloroethoxy)ethoxy)ethanol in the

presence of base to afford the alcohol 8. Tosylation ofthe alcohol 8 yielded the corresponding tosylate 9, whichwas then reacted with the phenol 1020 under basicconditions to produce the protected phenol 11. Subse-quent deprotection using standard procedures gave a 95%yield of the phenol 12, which was further alkylated with2-(2-(2-chloroethoxy)ethoxy)ethanol to produce the alco-hol 13, which was then reacted with tosyl chloride inthe presence of triethylamine and DMAP to give thetosylate 14.The unsymmetrical dumbbell compound 15, comprising

one hydroquinone ring and one resorcinol ring as theπ-electron-donating recognition sites, was constructed(Scheme 6) by coupling the phenol 6 and the monotosy-late 14 under mildly basic conditions.(24) Fitton, A. O.; Ramage, G. R. J. Chem. Soc. 1962, 4870-4874

Scheme 6

Scheme 7


The syntheses of the symmetrical dumbbell compoundswere achieved by following a similar synthetic strategy:it is outlined in Schemes 7 and 8. Resorcinol wasdialkylated with tosylate 9 under basic conditions to yieldthe protected bisphenol 16. Deprotection by hydro-genolysis of both benzyloxy groups afforded the corre-sponding bisphenol 17 which was then reacted with 2molar equiv of the tosylate 4 in the presence of base toproduce (Scheme 7) the symmetrical dumbbell compound18 containing one resorcinol ring sandwiched betweentwo hydroquinone rings within a polyether chain.The analogous symmetrical dumbbell compound 20,

comprised of two resorcinol rings sandwiching one hyd-roquinone ring within a polyether chain, was synthesized

(Scheme 8) in 60% by reaction under basic conditions of2 molar equiv of the phenol 6 with the bistosylate 19 toproduce the symmetrical dumbbell compound 20.

The self-assembly of the unsymmetrical [2]rotaxane23‚4PF6 was achieved (Scheme 9) in 11% yield by stirring1 molar equiv of the π-electron rich dumbbell compound15 in the presence of 3 molar equiv of the bipyridiniumsalt 21‚2PF6 and 1.2 molar equiv of 1,4-bis(bromometh-yl)benzene (22) in a DMF solution at room temperatureand ambient pressure (Scheme 9), followed by counterionexchange with NH4PF6/H2O to yield the hexafluorophos-phate salt 23‚4PF6. The mass spectrum (Figure 1) of23‚4PF6 reveals peaks corresponding to the molecular ion

Scheme 8

Scheme 9


and the molecular ion less one, two, and three hexafluro-phosphate counterions.

The symmetrical [2]rotaxanes 24‚4PF6 and 25‚4PF6,comprising the dumbbell components 18 and 20, respec-

Scheme 11

Scheme 10


tively, were self-assembled in 12% and 14% yields,employing conditions identical to those used for the self-assembly of the [2]rotaxane 23‚4PF6 (Schemes 10 and11).The yields of the [2]rotaxanes are relatively low in

comparision to the 32% yield reported for the self-assembly of the prototypical molecular shuttle18 in whichthe symmetrical linear dumbbell component contains twoπ-electron rich hydroquinone rings. Nonetheless, theyields of 23‚4PF6, 24‚4PF6, and 25‚4PF6 seem to be ofsimilar magnitudes to those reported for the self-as-sembly of other molecular shuttles in which one of thehydroquinone rings is replaced by a different π-electronrich unit.It can be concluded that the presence of the meta-

substituted resorcinol ring in the linear polyether chainundermines the efficiency of the self-assembly processeswhen compared to the reference situation where onlypara-substituted hydroquinone rings are present in thedumbbell components. Nevertheless, the decrease in theefficiency of the self-assembly process is not as dramaticas that observed for the related [2]catenanes. Thisdifference undoubtedly reflects the inclusion of a meta-substituted benzene ring in the macrocyclic polyethercomponent which forces the crown ether to adopt aconformation that disrupts the molecular recognitionbetween the individual molecular precursors, thus hin-dering the self-assembly process. On the other hand, thedumbbell component possesses much more conforma-tional freedom than do the macrocyclic polyether analogs,and so the inclusion of meta-substituted benzenoid rings

in a linear system does not affect the self-assemblyprocesses as much as that in the case of a [2]catenane.

1H NMR Spectroscopy. The 1H NMR spectra re-corded for the [2]rotaxanes 23‚4PF6, 24‚4PF6, and 25‚4PF6

exhibit marked temperature dependencies in accordancewith the highly fluxional solution state structures ex-pected for mechanically-interlocked compounds.The 1H NMR spectrum (400 MHz, CD3COCD3) of

23‚4PF6 at room temperature (Figure 2) shows largelybroadened or averaged signals. In particular, only oneresonance is observed for each of the R and â protons onthe bipyridinium units of the tetracationic cyclophane.Process 1, i.e., the shuttling of the tetracationic cyclo-phane back and forth between the nondegenerate π-elec-tron rich recognition sites (Scheme 9), is thereforeoccurring at a rate comparable to or greater than that ofthe 400 MHz 1H NMR time scale at ambient tempera-tures. Upon cooling of the solution, the spectra sharpen(Figure 3) initially such that, at 240 K, resonancesattributable to the major translational isomer 1, i.e., thespecies in which the tetracationic cyclophane resides onthe hydroquinone station, are well resolved. The assign-ment of the resonances was assisted by two-dimensionalCOSY and NOESY experiments. The correspondingresonances expected for the minor translational isomer2 are, however, broad and indistinct by comparison. Thereason for this phenomenom is probably associated inpart with a further site-exchange process occurring as aresult of the included resorcinol ring departing from thecavity of the tetracationic cyclophane, re-orienting itself,and re-entering the cavity.

Figure 2. Partial 1H NMR spectrum of 23‚4PF6 in CD3COCD3 at 304 K.


Relative recognition-site occupancies were calculatedby comparison of the net integral intensities of theisolated resonances observed for the major translationalisomer with the total integral intensity of the character-istic chemical shift region for the R-protons on thebipyridinium units (Figure 4). Specifically, the signalscorresponding to the unoccupied resorcinol station showthe expected apparent triplet (Ha), two double doublets

(Hb and Hd), and a further apparent triplet (Hc) resonat-ing at δ 5.87 (J ≈ 1 Hz), δ 6.15 and 6.35, and δ 6.85 (J ≈7 Hz), respectively. Similarly, resonances correspondingto the protons of the linking phenylene rings within thetetraarylmethane stoppers appear as two different AA′XX′systems, resonating at δ 6.58 and 6.97 and δ 6.97 and7.20, respectively. The isolated resonances were com-pared to the overlapping resonances for the R-protons ofthe bipyridinium units, as illustrated in Figure 4. Thisregion shows the two doublets expected for the chemicallynonequivalent R-protons of the bipyridinium units in thedesymmetrized tetracationic cyclophane associated withthe major translational isomer, resonating on top of abroad signal attributable to the minor translationalisomer. As this region must account for all the tetraca-tionic cyclophane present in both translational isomersof the [2]rotaxane, a not unreasonable estimate of therelative concentration of the minor translational isomerpresent in the solution at this temperature can beobtained by simple subtraction of the appropriately-weighted integral intensity. Thus, the relative recogni-tion-site occupancy for the tetracationic cyclophane of the[2]rotaxane 23‚4PF6 in CD3COCD3 solution at 240 K wascalculated as 2:1 in favor of hydroquinone occupancy overthat of resorcinol occupancy.Unfortunately, further cooling of the solution resulted

in only further broadening of the resonances to the extentthat, at temperatures around 200 K (400 MHz), nosignals were clearly resolved. The increasing complexityof the spectra with decreasing temperature could resultfrom the system folding itself (Scheme 12) in order to

Figure 3. Partial 1H NMR spectrum of 23‚4PF6 in CD3COCD3 at 240 K.

Figure 4. Partial 1H NMR spectrum of 23‚4PF6 in CD3COCD3

at 240 K depicting the shift region of the R-bipyridiniumprotons and the region for the resorcinol Ha proton.


maximize the effectiveness of the “alongside” interactionbetween the tetracationic cyclophane and the unoccupiedπ-electron rich recognition site. Resolution of this issuecould only be accomplished using much higher fieldstrengths and has not been explored further here. It isnoteworthy, however, that the relative site occupancyobserved for the analogous [2]catenane23sa system inwhich the two π-electron rich components are incorpo-rated into a crown ether ring and are thus preorganizedfor efficient “inside” and “alongside” complexation of thetetracationic cyclophanesis much more strongly weightedin favor of hydroquinone occupation at the expense ofresorcinol occupation.The behavior of the three-station [2]rotaxane 24‚4PF6

is very similar to that of 23‚4PF6. The main differencecomes from the symmetrical nature of the dumbbellcomponent of 24‚4PF6, comprising two degenerate hyd-roquinone stations. The shuttling of the tetracationiccyclophane gives rise to two different translationalisomers, 1 and 2, as depicted in Scheme 10. The 1H NMRspectrum (400 MHz, CD3COCD3) of 24‚4PF6 at 240 K(Figure 5) shows well-resolved resonances attributableto the major translational isomer 1. The signals corre-sponding to the protons of the unoccupied resorcinol ringcan also be observed: they are an apparent triplet (Ha)at δ 5.70 (J ≈ 1 Hz), two overlapping double doublets(Hb/d) centered on δ 6.25, and another apparent triplet(Hc) centered on δ 6.84 (J ≈ 7 Hz). The signals for theprotons corresponding to the linking phenylene ringswithin the tetraarylmethane stoppers resonate as twodifferent AA′XX′ (He/f and Hg/h) systems with δ 7.15 and6.91 and δ 6.96 and 6.57. These two AA′XX′ systemscorrespond to the major translational isomer 1, wherethe tetracationic cyclophane is residing on one of thedegenerate hydroquinone rings. No isolated resonancesfor the minor translational isomer 2 can be observed. Therelative recognition-site occupancy for the tetracationiccyclophane in 24‚4PF6 in CD3COCD3 at 240 K wascalculated in the same fashion as for that described in23‚4PF6. It revealed a 4:1 ratio in favor of translationalisomer 1 over translational isomer 2.

The three-station [2]rotaxane 25‚4PF6, in which ahydroquinone station is sandwiched between two resor-cinol units, behaves in a manner similar to the [2]rotax-anes 23‚4PF6 and 24‚4PF6. The 1H NMR spectrumrecorded in CD3COCD3 at 220 K (400 MHz) shows well-resolved resonances for the protons corresponding to thealongside resorcinol rings. A broad apparent singlet (Ha)at δ 5.88, two double doublets (Hd/b) at δ 6.13 and 6.45,and an apparent triplet (Hc) at δ 7.18 (J ≈ 7 Hz),corresponding to the major translational isomer 1 (Scheme11), where the hydroquinone ring is included within thecavity of the tetracationic cyclophane, are observed. Thesignals corresponding to the linking phenylene ringswithin the tetraarylmethane stoppers resonate as asingle AA′BB′ (He/f) system at δ 6.98 and 7.16 for themajor translational isomer, indicating the presence of asymmetrical [2]rotaxane. The relative recognition-siteoccupancy calculated for 25‚4PF6 in CD3COCD3 at 220K was 8:1 in favor of translational isomer 1 overtranslational isomer 2. This high selectivity can beexplained on the basis of the most favored geometry insolution (Scheme 12), wherein the tetracationic cyclo-phane resides around the central hydroquinone ring,leaving the two π-electron deficient bipyridinium unitsof the tetracationic cyclophane to interact in an “exo”fashion with the two alongside π-electron rich resorcinolrings, resulting in the tetracationic cyclophane beingsandwiched by the two “free” resorcinol rings, as observedin other linear pseudorotaxane systems.23b By adoptingthis geometry, the rotaxane gains some extra stabilizinginteractions.

Conclusions

The self-assembly of three novel [2]rotaxanes, 23‚4PF6-25‚4PF6, containing resorcinol and hydroquinone sta-tions, has been achieved in reasonable yields (11-12%).Although these yields are lower than that (32%) for theself-assembly of a [2]rotaxane comprising two hydro-quinone rings in the dumbbell component,18 they aresimilar to those obtained when one of the hydroquinonerings is replaced by another π-electron rich station.19-21

Scheme 12


There is a decrease in the efficiency of the self-assemblyprocess when one of the hydroquinone stations is replacedby a resorcinol one, but the effect is not as dramatic asthat observed in the case of the corresponding [2]cat-enane system.The variable temperature 1H NMR spectroscopic stud-

ies reveal that [2]rotaxanes 23‚4PF6-25‚4PF6 exist astwo different translational isomers in all three cases. Thetwo-station [2]rotaxane 23‚4PF6 displays an approxi-mately 2:1 selectivity for the major translational isomer1 over the translational isomer 2. The three-station[2]rotaxane 24‚4PF6 shows a selectivity of approximately4:1. The difference in selectivity can be explained easilyon the basis that the [2]rotaxane possesses two hydro-quinone stations and only one resorcinol one. Finally,the three-station [2]rotaxane 25‚4PF6 exhibits the highestselectivity of 8:1 as a result of folding in solution (Scheme12) in order to maximize the alongside noncovalent

bonding interactions (Table 1). The [2]rotaxane 25‚4PF6

enjoys the highest selectivity of one translational isomerover the other, and therefore it represents the first stepin the construction of abacus-like molecular structureswith switching capabilities that could be controlled byexternal stimuli.The isomer selectivities observed for the linear [2]ro-

taxanes are not nearly as high as that for the analogous[2]catenane 2‚4PF6. This observation is an interestingone that merits further investigation by computationalmethods. These investigations are underway.

Experimental Section

General Procedures. Solvents were used as supplied,with the exception of the following: dimethylformamide (DMF)was distilled from calcium hydride under reduced pressure andacetonitrile (MeCN) was distilled under nitrogen from calciumhydride. Developed thin layer chromatography (TLC) plateswere air-dried, scrutinized under a UV lamp, and, if necessary,then either sprayed with cerium(IV)sulfate-sulfuric acidreagent and heated to ca. 100 °C or developed in an iodinetank. Microanalyses were performed by the University ofSheffield Microanalytical Service. Melting points were deter-mined in an open capillary tube and are uncorrected. 1Hnuclear magnetic resonance (NMR) spectra were recorded ateither 300 or 400 MHz using the deuterated solvent as a lockand residual protonated solvent or tetramethylsilane as aninternal reference. 13C NMR spectra were recorded at either75 or 100 MHz.3-(Benzyloxy)phenol24 (3). A solution of resorcinol (50 g,

450 mmol) and K2CO3 (6.21 g, 45 mmol) in dry MeCN (200

Figure 5. Partial 1H NMR spectrum of the [2]rotaxane 24‚4PF6 in CD3COCD3 at 240 K.

Table 1. Relative Site Occupancy forResorcinol-Containing Molecular Assemblies As

Determined by 1H NMR Spectroscopy

compound solventtemperature

(K)site

occupancya

2‚4PF6 CD3COCD3 253 98:223‚4PF6 CD3COCD3 240 2:124‚4PF6 CD3COCD3 240 4:125‚4PF6 CD3COCD3 220 8:1a The site occupancy is always such that the major translational

isomer has the cyclobis(paraquat-p-phenylene) tetracationic com-ponent encircling the hydroquinone ring in the other component.


mL) was refluxed under nitrogen for 1 h. A solution of benzylbromide (7.7 g, 0.045 mol) in dry MeCN (250 mL) was addeddropwise over 1 h to the reaction mixture, the solution wasallowed to reflux for 4 days under nitrogen with vigorousstirring. The solution was cooled down to room temperatureand filtered, and the solvent was removed in vacuo. Theresidual oil was taken up in CH2Cl2 (200 mL) and washed withdilute aqueous HCl (pH 3, 2 × 200 mL) and then brine (2 ×200 mL). The organic phase was dried (MgSO4) and thesolvent removed in vacuo. Column chromatography (SiO2,CH2Cl2) afforded the phenol 3 as a white solid (6.29 g, 70%):mp 51-51.8 °C (lit.24 mp 50-51 °C); IR (NaCl) 3424, 3031,2936, 2872, 2433, 1594, 1498, 1490, 1454, 1381, 1238, 1216,1146, 1080, 1026, 940, 838, 764, 696 cm-1; EIMS 200 (M+); 1HNMR (CDCl3, 300 MHz, 25 °C) δ 5.01 (s, 2H), 6.12 (s, 1H),6.49-6.47 (dd, 1H, J ) 7, 1 Hz), 6.62-6.60 (dd, 1H, J ) 7, 1Hz), 7.15 (t, 1H, J ) 7 Hz), 7.45-7.34 (m, 5H); 13C NMR(CDCl3, 75 MHz) δ 70.2, 102.7, 107.5, 108.4, 127.6, 128.1,128.7, 130.3, 136.9, 156.8, 160.2.1-[2-(2-(2-(Tritylphenoxy)ethoxy)ethoxy)ethoxy]-3-(ben-

zyloxy)benzene (5). A solution of 3-(benzyloxy)phenol (3)(1.79 g, 8.9 mmol), K2CO3 (1.8 g, 13 mmol), and a catalyticamount of LiBr in dry MeCN (100 mL) was mixed and heatedunder reflux for 1 h in a nitrogen atmosphere. A solution oftosylate20 4 (5.58 g, 8.9 mmol) in dry MeCN (100 mL) wasadded dropwise over 30 min to the reaction mixture; thesolution was heated under reflux for 4 days under nitrogenwith vigorous stirring. The solution was allowed to cool to rtbefore it was filtered and the solvent removed in vacuo. Theresidual oil was dissolved in CH2Cl2 (200 mL) and washed withdilute HCl (pH 3, 2 × 200 mL) and brine (2 × 200 mL). Theorganic phase was dried (MgSO4) and the solvent removed invacuo to yield the protected phenol 5 as a yellow oil (4.82 g,84%): IR (NaCl) 3056, 2924, 2873, 1594, 1508, 1491, 1448,1250, 1182, 1154, 829, 748, 702 cm-1; LSIMS m/z 650 (M+);1H NMR (CDCl3, 300 MHz, 25 °C) δ 3.78 (s, 4H), 3.90-3.86(m, 4H), 4.15-4.12 (m, 4H), 5.06 (s, 2H), 6.57-6.54 (dd, 1H,J ) 7, 1 Hz), 6.62-6.60 (m, 2H), 6.83-6.80 (AA′BB′ system,2H, J ) 8 Hz), 7.14-7.11 (AA′BB′ system, 2H, J ) 8 Hz), 7.30-7.19 (m, 16H), 7.48-7.35 (m, 5H); 13C NMR (CDCl3, 75 MHz)δ 64.3, 67.3, 67.5, 69.8, 70.0, 70.8, 102.1, 107.2, 107.4, 113.4,125.9, 127.4, 127.5, 127.9, 128.6, 129.9, 131.1, 132.2, 139.2,147.1, 156.8, 160.0; HRMS calcd for C44H42O5 [M]+ 650.3032,found 650.3041 (err -1.3 ppm).1-[2-(2-(2-(Tritylphenoxy)ethoxy)ethoxy)ethoxy]-3-hy-

droxybenzene (6). A solution of 5 (5.57 g, 8.7 mmol) inCHCl3 (200 mL) was added to a suspension of Pd/C (5%, 1.5g) in MeOH (200 mL). The suspension was stirred for 12 h ashydrogen gas was bubbled into the mixture. The suspensionwas filtered through Celite, and the solvent was removed invacuo to produce phenol 6 as a white solid (4.66 g, 97%).Phenol 6 is prone to oxidation, and so the next reaction wascarried out immediately using the crude product.1-[2-(2-(2-Hydroxyethoxy)ethoxy)ethoxy]-4-(ben-

zyloxy)benzene20 (8). A stirred suspension of 4-(benzyl-oxy)phenol (15 g, 75 mmol) and K2CO3 (35 g, 250 mmol) indry MeCN (250 mL) was brought to reflux under nitrogen. 2-(2-(2-Chloroethoxy)ethoxy)ethanol (22 mL) was added dropwise,and the resulting mixture was stirred at reflux under nitrogenfor 3 days. The suspension was filtered and the solvent re-moved in vacuo. CH2Cl2 (200 mL) was added to the residue;the resultant mixture was washed with dilute HCl (pH 3, 3 ×250 mL) and then distilled H2O (3 × 250 mL). The organicphase was dried (MgSO4) and the solvent removed in vacuo,yielding product 8 as a white powder (21.05 g, 84%): mp 49-50 °C; IR (NaCl) 3298, 2935, 2879, 1511, 1452, 1237, 1115,1066, 1029, 952, 833, 737 cm-1; EIMS m/z 332 (M+); 1H NMR(CDCl3, 300 MHz, 25 °C) δ 3.50-3.63 (m, 2H), 3.68-3.74 (m,4H), 3.82-3.85 (t, 2H), 4.07-4.10 (m, 4H), 5.01 (s, 2H), 6.83-6.91 (m, 4H), 7.28-7.44 (m, 5H); 13C NMR (CDCl3, 75 MHz) δ61.8, 68.1, 69.9, 70.4, 70.7, 70.8, 72.5, 115.7, 115.8, 127.5, 127.9,128.5, 137.3, 153.1, 153.2; HRMS calcd for C19H24O5 [M]+332.1623, found 332.1616 (err 2.3).1-[2-(2-(2-(p-Toluenesulfonyloxy)ethoxy)ethoxy)ethoxy]-

4-(benzyloxy)benzene (9). A solution of the alcohol 8 (3 g,9.2 mmol), Et3N (3.78 mL, 37.4 mmol), and a catalytic amount

of DMAP in dried CH2Cl2 was prepared and cooled to 0 °Cunder nitrogen. A solution of p-toluenesulfonyl chloride (2.07g, 10 mmol) in dry CH2Cl2 (300 mL) was added dropwise withcontinuous stirring over 2 h to the reaction mixture; thesolution was allowed to warm up to rt while being stirredunder nitrogen for 4 h. The solution was filtered and thesolvent removed in vacuo. CH2Cl2 (200 mL) was added to theresidue, and the solution was washed with dilute HCl (pH 3,2 × 250 mL) and distilled H2O (2 × 250 mL). The organiclayer was dried (MgSO4) and the solvent was removed in vacuoto yield a yellow oil which was recrystallized from hexane:EtOAc (8:2) to give a pale yellow powder. This powder waswashed thoroughly with hexane to give product 9 as a whitepowder (3.7 g, 82%): mp 52-52 °C; IR (NaCl) 2869, 2360, 1597,1506, 1353, 1189, 1175, 1096, 920, 712, 662 cm-1; LSIMS 486(M+); 1H NMR (CDCl3, 300 MHz, 25 °C) δ 2.43 (s, 3H), 3.59-3.62 (m, 2H), 3.64-3.71 (m, 6H), 3.78-3.81 (m, 2H), 4.04-4.07 (m, 2H), 5.01 (s, 2H), 6.82-6.92 (m, 4H), 7.31-7.44 (m,7H), 7.79-7.81 (AA′BB′ system, 2H, J ) 8 Hz); 13C NMR(CDCl3, 75.5 MHz) δ 21.6, 68.1, 68.7, 69.2, 69.9, 70.7, 70.8,70.8, 115.6, 115.8, 127.5, 127.9, 128.0, 128.5, 129.8, 133.1,137.3, 144.8, 153.2; HRMS calcd for C26H30O7S [M]+ 486.1712,found 486.1700 (err 2.5).1-[2-(2-(2-(Tritylphenoxy)ethoxy)ethoxy)ethoxy]-4-(ben-

zyloxy)benzene (11). A stirred suspension of the vacuum-dried tritylphenol (10) (1.64 g, 5 mmol) and K2CO3 (2.86 g,20.7 mmol) in dry MeCN (12 mL) was brought to reflux undernitrogen. A solution of tosylate 9 (2 g, 4.11 mmol) in dry MeCN(15 mL) was added dropwise over 30 min. The resultingmixture was stirred for 4 days at 80 °C under nitrogen. Thecream-colored suspension was filtered and the solvent removedin vacuo. The residual oil was taken up in CH2Cl2 (100 mL)and washed with dilute HCl (pH 3, 3 × 100 mL) and distilledH2O (3 × 100 mL). The organic phase was dried (MgSO4) andthe solvent removed in vacuo to yield a yellow oil. Columnchromatography (SiO2, CH2Cl2) afforded 11 as a white solid(2.19 g, 45%): mp 80.8-81 °C; IR (NaCl) 3056, 3030, 2920,2871, 1507, 1452, 1229, 1125, 826, 747, 702 cm-1; EIMS m/z650 (M+); 1H NMR (CDCl3, 300 MHz, 25 °C) δ 3.77 (s, 4H),3.84-3.88 (m, 4H), 4.08-4.14 (m, 4H), 5.01 (s, 2H), 6.81-6.84(AA′BB′ system, 2H, J ) 8 Hz), 6.85-6.93 (m, 4H), 7.11-7.14(AA′BB′ system, 2H, J ) 8 Hz), 7.18-7.46 (m, 20H); 13C NMR(CDCl3, 75 MHz) δ 64.4, 67.3, 68.1, 69.9, 70.0, 70.7, 70.9, 113.4,115.7, 115.9, 125.9, 126.2, 127.5, 127.5, 127.9, 128.6, 131.2,132.2, 137.3, 139.2, 147.1, 153.2, 153.2, 156.8. Anal. Calcdfor C44H42O5: C, 81.20; H, 6.50. Found: C, 81.02; H, 6.70.1-[2-(2-(2-(Tritylphenoxy)ethoxy)ethoxy)ethoxy]-4-hy-

droxybenzene (12). A solution of 11 (1.55 g, 2.38 mmol) inCH2Cl2 (125 mL) was added to a suspension of Pd/C (5%, 0.31g) in MeOH (125 mL). H2 gas was bubbled through themixture with continuous stirring for 15 h. The solution wasfiltered through Celite. The solvent was removed in vacuo toyield 12 as a white solid (1.24 g, 95%). This product wasunstable, and so the next reaction was carried out immediatelyusing the crude product.1-[2-(2-(2-(Tritylphenoxy)ethoxy)ethoxy)ethoxy]-4-[2-

(2-(2-hydroxyethoxy)ethoxy)ethoxy]benzene19 (13). Astirred suspension of 12 (1.24 g, 2.21 mmol) and K2CO3 (4.36g, 31.5 mmol) in MeCN (40 mL) was brought to reflux undernitrogen with continuous stirring. 2-(2-(2-Chloroethoxy)-ethoxy)ethanol (2.74 mL, 14.8 mmol) was added dropwise, andthe resulting mixture was heated under reflux under nitrogenfor 3 days. The solution was cooled and filtered, and thesolvent was removed in vacuo. CH2Cl2 (200 mL) was addedto the residue, and the resultant mixture was washed withdilute HCl (pH 3, 2 × 250 mL) and then distilled H2O (2 ×250 mL). The organic phase was dried (MgSO4) and thesolvent removed in vacuo to yield a yellow oil. Columnchromatography [SiO2, CH2Cl2:MeOH (98.5:1.5)] gave 13 as ayellow oil, which was crystallized from hexane and washedthoroughly with hexane:EtOAc (5:2) to yield the title compoundas a pale yellow solid (1.2 g, 69%): mp 49-50 °C; IR (NaCl)3420, 3057, 3029, 2874, 2360, 2340, 1508, 1490, 1234, 1183,1123, 1066, 939, 750, 702 cm-1; LSIMSm/z 692 (M+); 1H NMRδ (CDCl3, 300 MHz, 25 °C) δ 3.61-3.67 (m, 6H), 3.70-3.76(m, 6H), 3.82-3.88 (m, 6H), 4.06-4.12 (m, 6H), 6.77-6.8


(AA′BB′ system, 2H, J ) 8 Hz), 6.83 (s, 4H), 7.07-7.10 (AA′BB′system, 2H, J ) 8 Hz), 7.18-7.26 (m, 15H); 13C NMR (CDCl3,75.5 MHz) δ 42.7, 61.8, 64.3, 67.3, 68.2, 69.8, 69.9, 69.9, 70.4,70.8, 70.9, 72.5, 113.4, 115.6, 125.9, 127.4, 131.1, 132.2, 139.2,147.1, 153.1. Anal. Calcd for C43H48O8: C, 74.54; H, 6.98.Found: C, 74.56; H, 6.94.1-[2-(2-(2-(p-Toluenesulfonyloxy)ethoxy)ethoxy)ethoxy]-

4-[2-(2-(2-(tritylphenoxy)ethoxy)ethoxy)ethoxy]-benzene (14). A stirred solution of the vacuum-dried 13 (0.4g, 0.5 mmol), Et3N (0.8 mL, 8 mmol), and a catalytic amountof DMAP in dry CH2Cl2 (20 mL) was cooled to 0 °C under anitrogen atmosphere. A solution of p-toluenesulfonyl chloride(0.14 g, 0.55 mmol) in dry CH2Cl2 (10 mL) was added dropwiseover 30 min. The resultant mixture was left stirring at 0 °Cfor 2 h. The solution was warmed up to room temperatureand then filtered, and the solvent was removed in vacuo togive a yellow oil. This oil was dissolved in CH2Cl2 (100 mL)and washed with dilute HCl (pH 3, 2 × 100 mL) and distilledH2O (2 × 100 mL). The organic phase was dried (MgSO4) andthe solvent removed in vacuo to yield a pale yellow oil. Columnchromatography [SiO2, CH2Cl2:MeOH (99:1)] afforded 14 as ayellow oil (0.1 g, 41%): IR (NaCl) 3055, 2923, 1598, 1508, 1453,1356, 1232, 1176, 1124, 1010, 924, 816, 704 cm-1; LSIMSm/z846 (M+); 1H NMR (CDCl3, 300 MHz, 25 °C) δ 2.41 (s, 3H),3.59-3.81 (m, 18H), 4.02-4.17 (m, 8H), 6.76-6.79 (AA′BB′system, 2H, J ) 8 Hz), 6.81-6.83 (m, 4H), 7.07-7.10 (AA′BB′system, 2H, J ) 8 Hz), 7.13-7.25 (m, 15H), 7.29-7.31 (AA′BB′system, 2H, J ) 6 Hz), 7.58-7.61 (AA′BB′ system, 2H, J ) 6Hz); 13C NMR (CDCl3, 75 MHz) δ 21.6, 42.8, 61.8, 64.3, 67.3,68.1, 68.8, 69.9, 70.4, 70.8, 70.8, 70.9, 71.4, 72.5, 113.4, 115.7,125.9, 127.4, 128.0, 129.7, 129.8, 131.1, 132.2, 133.1, 139.2,144.8, 147.1, 153.1, 153.2, 156.8. Anal. Calcd for C50H54-O10S: C, 70.90; H, 6.43; S, 3.78. Found: C, 71.02; H, 6.21; S,3.90.1-{p-[2-(2-(2-(4-Tritylphenoxy)ethoxy)ethoxy)-

ethoxy]phenoxy}-10-{m-[2-(2-(2-(4-tritylphenoxy)-ethoxy)ethoxy)ethoxy]phenoxy}-3,6-dioxaoctane (15). Asolution of phenol 6 (0.58 g, 1.04 mmol), K2CO3 (1g, 7.2 mmol),and a catalytic amount of LiBr in dry MeCN (100 mL) washeated under reflux over 1 h under a nitrogen atmosphere. Asolution of tosylate 14 (0.88 g, 1.04 mmol) in dry MeCN (70mL) was added dropwise over 30 min to the previous solution.The resulting mixture was heated under reflux for 5 daysunder nitrogen with vigorous stirring. The solution was cooleddown to rt and then filtered, and the solvent was removed invacuo. The residual oil was then dissolved in CH2Cl2 (200 mL)and washed with dilute HCl (pH 3, 2 × 200 mL) and brine(2 × 200 mL). The organic phase was dried (MgSO4) and thesolvent removed in vacuo to give a brown oil. Columnchromatography [SiO2, CH2Cl2:MeOH (99:1)] yielded dumbbellcompound 15 as a brown oil (0.91 g, 71%): IR (NaCl) 3054,3029, 2922, 2873, 1606, 1508, 1492, 1448, 1230, 1185, 1128,1065, 948, 827, 748, 703 cm-1; LSIMSm/z 1234 (M+); 1H NMR(CDCl3, 300 MHz, 25 °C) δ 3.76 (s, 12H), 3.87-3.86 (m, 12H),4.12-4.09 (m, 12H), 6.54-6.52 (m, 2H), 6.83-6.80 (AA′BB′system, 4H, J ) 8 Hz), 6.86-6.85 (m, 4H), 7.14-7.11 (AA′BB′system, 4H, J ) 8 Hz), 7.29-7.18 (m, 32 H); 13C NMR (CDCl3,75 MHz) δ 30.2, 64.1, 67.1, 67.2, 67.9, 69.6, 69.8, 70.7, 71.1,72.3, 101.6, 106.9, 113.2, 115.4, 125.7, 127.3, 128.4, 129.7,131.0, 132.0, 139.0, 146.9, 152.9, 153.4, 156.6, 159.8; HRMScalcd for C80H82O12 [M]+ 1234.5806, found 1234.5831 (err -2.0).1 , 3 -B i s [ 2 - ( 2 - ( 2 - ( 4 - ( ( b en zy l o xy ) phenoxy ) -

ethoxy)ethoxy)ethoxy]benzene (16). A solution of resor-cinol (0.24 g, 2.2 mmol), K2CO3 (1.5 g, 10.8 mmol), and acatalytic amount of LiBr in dry MeCN (50 mL) was broughtto reflux for 1 h in a nitrogen atmosphere. A solution oftosylate 9 (2.12 g, 4.4 mmol) in dry MeCN (150 mL) was addeddropwise over 30 min to the reaction mixture; the solution wasrefluxed under nitrogen for 5 days with vigorous stirring. Thesolution was cooled to rt and filtered, and the solvent wasremoved in vacuo. The residual oil was dissolved in CH2Cl2(200 mL) and washed with dilute HCl (pH 3, 2 × 200 mL) andbrine (2 × 200 mL). The organic phase was dried (MgSO4)and the solvent removed in vacuo. Column chromatography[SiO2, EtOAc:hexane (40:60) and then CH2Cl2:MeOH (98:2)]yielded diprotected bisphenol 16 as a yellow oil (2.0 g, 62%):

IR (NaCl) 3062, 3032, 2924, 2872, 1593, 1507, 1454, 1289,1228, 1124, 924, 826, 741, 697 cm-1; LSIMS m/z 738 (M+); 1HNMR (CDCl3, 300 MHz, 25 °C) δ 3.73 (s, 8H), 3.84-3.80 (m,8H), 4.09-4.04 (m, 8H), 4.98 (s, 4H), 6.51-6.49 (m, 3H), 6.86-6.84 (m, 8H), 7.13 (t, 1H, J ) 7 Hz)), 7.42-7.24 (m, 10H); 13CNMR (CDCl3, 75 MHz) δ 61.8, 67.4, 68.1, 69.8, 69.9, 70.7, 70.9,102.4, 106.9, 107.2, 108.1, 115.7, 115.9, 127.5, 127.9, 128.6,130.0, 137.3, 153.2; HRMS calcd for C44H50O10 [M]+ 738.3440,found 738.3411 (err -1.0).1,3-Bis[2-(2-(2-(4-hydroxyphenoxy)ethoxy)ethoxy)-

ethoxy]benzene (17). A solution of compound 16 (0.580 g,0.78 mmol) in CHCl3 (100 mL) was added to a suspension ofPd/C (5%, 1 g) in MeOH (100 mL). The resulting suspensionwas stirred at rt for 10 h as H2 gas was bubbled into themixture. The suspension was then filtered through Celite andthe solvent removed in vacuo to give the bisphenol 17 as awhite solid (0.42 g, 95%). Since compound 17 is unstable, thenext reaction was carried out immediately using the crudeproduct.1,3-Bis{2-(2-(2-[4-tritylphenoxy)ethoxy)ethoxy)-

ethoxy]phenoxy]ethoxy)ethoxy)ethoxy}benzene (18). Asolution of the biphenol 17 (0.41 g, 0.73 mmol), K2CO3 (1 g,7.2 mmol), and a catalytic amount of LiBr in dry MeCN (70mL) was refluxed for 1 h under nitrogen. A solution of tosylate4 (1.14 g, 1.84 mmol) in dry MeCN (100 mL) was addeddropwise over 30 min to the reaction mixture; the solution washeated under reflux for 5 days in a nitrogen atmosphere withvigorous stirring. The solution was then allowed to cool downto rt before it was filtered and the solvent removed in vacuo.The residual oil was dissolved in CH2Cl2 (200 mL) before beingwashed with dilute HCl (pH 3, 2 × 200 mL) and brine (2 ×200 mL). The organic phase was dried (MgSO4) and thesolvent removed in vacuo. Column chromatography [SiO2,CH2Cl2:MeOH (98:2)] afforded the dumbbell compound 18 asa brown oil (1.07 g, 71%): IR (NaCl) 3054, 3030, 2874, 1597,1510, 1452, 1240, 1183, 1136, 949, 827, 740, 700 cm-1; LSIMSm/z 1460 (M + H)+; 1H NMR (CDCl3, 300 MHz, 25 °C) δ 3.72(s, 16H), 3.89-3.85 (m, 16H), 4.14-4.08 (m, 16H), 6.55-6.52(m, 3H), 6.83-6.80 (AA′BB′ system, 4H, J ) 8 Hz), 6.86-6.85(m, 8H), 7.14-7.11 (AA′BB′ system, 4H, J ) 8 Hz), 7.29-7.19(m, 31H); 13C NMR (CDCl3, 75 MHz) δ 53.5, 61.8, 64.3, 67.3,67.4, 68.1, 69.8, 69.9, 70.9, 72.5, 101.8, 107.1, 113.4, 115.6,123.4, 125.9, 127.5, 128.6, 129.9, 131.1, 132.2, 139.2, 147.1,153.1, 156.7, 160.0. Anal. Calcd for C92H98O16: C, 75.68; H,6.77. Found: C, 75.62; H, 6.87.1,4-Bis{2-(2-(2-[3-[2-(2-(2-(4-tritylphenoxy)ethoxy)-

ethoxy)ethoxy]phenoxy]ethoxy)ethoxy)ethoxy}-benzene (20). A solution of the phenol 6 (4.29 g, 7.6 mmol),K2CO3 (3 g, 21 mmol), and a catalytic amount of LiBr in dryMeCN (150 mL) was heated under reflux for 1 h in a nitrogenatmosphere. A solution of the bistosylate 19 (2.61 g, 3.8 mmol)in dry MeCN (150 mL) was added dropwise over 30 min tothe reaction mixture; the solution was refluxed under nitrogenfor 7 days with vigorous stirring. The solution was thenallowed to cool down to rt before it was filtered and the solventremoved in vacuo. The residual oil was dissolved in CH2Cl2and washed with dilute HCl (pH 3, 2 × 200 mL) and then brine(2 × 200 mL). The organic phase was dried (MgSO4) and thesolvent removed in vacuo. Column chromatography [(SiO2,CH2Cl2:MeOH (99:1) and then CH2Cl2:MeOH (98:2)] affordedthe dumbbell compound 20 as a brown oil (3.33 g, 60%): IR(NaCl) 3054, 3029, 2923, 2873, 1594, 1507, 1492, 1448, 1233,1185, 1126, 946, 827, 748, 703 cm-1; LSIMS m/z 1460 (M +H)+; 1H NMR (CDCl3, 300 MHz, 25 °C) δ 3.72 (s, 16H), 3.89-3.84 (m, 16H), 4.14-4.07 (m, 16H), 6.53-6.51 (m, 6H), 6.83-6.80 (AA′BB′ system, 4H, J ) 8 Hz), 6.86-6.85 (m, 4H), 7.13-7.10 (AA′BB′ system, 4H, J ) 8 Hz), 7.29-7.19 (m, 32H); 13CNMR (CDCl3, 75 MHz) δ 30.4, 42.8, 64.4, 67.3, 67.5, 68.1, 69.8,70.0, 70.1, 70.1, 71.3, 71.4, 101.9, 107.2, 113.4, 115.7, 125.9,127.5, 129.9, 131.2, 132.2, 139.2, 147.1, 153.2, 156.8, 160.0.Anal. Calcd for C92H98O16: C, 75.68; H, 6.77. Found: C, 75.67;H, 6.68.

{[2]-[1-{p-[2-(2-(2-(4-Tritylphenoxy)ethoxy)ethoxy)-ethoxy]phenoxy}-10-{m-[2-(2-(2-(4-tritylphenoxy)ethoxy-)ethoxy)ethoxy]phenoxy}-3,6-dioxaoctane][9,18,29,38-tetraazonia[1.1.0.1.1.0]paracyclophane]rotaxane} Tet-rakis(hexafluorophosphate) (23‚4PF6). A solution of the


dumbbell compound 15 (0.503 g, 0.4 mmol), the bipyridiniumsalt 21‚2PF6 (0.086 g, 1.2 mmol), and the dibromide 22 (0.38g, 1.4 mmol) in dry DMF (10 mL) was stirred for 10 days atroom temperature and pressure. Thereafter, Et2O (50 mL)was added to the reaction mixture in order to precipitate allthe charged species. The orange precipitate was filtered andwashed with Et2O (50 mL) and CH2Cl2 (50 mL). Columnchromatography [SiO2, MeOH:NH4Cl (2 M):MeNO2 (7:2:1)]afforded the rotaxane 23‚4PF6 as a red solid in the form ofthe chloride salt. The red solid was dissolved in H2O, and asaturated aqueous solution of NH4PF6 was added dropwiseuntil no further precipitation was observed. The red precipi-tate was filtered off and washed thoroughly with H2O to yieldrotaxane 23‚4PF6 as a red powder (100 mg, 11%) after vacuumdrying: mp > 250 °C dec; IR (NaCl) 3055, 2921, 2360, 1636,1594, 1508, 1452, 1247, 1183, 1151, 841, 699 cm-1; UV/vis λmax(ε) 252 nm (37500), 463 nm (328); LSIMSm/z 2336 (M+), 2191(M - PF6)+, 2046 (M - 2PF6)+, 1900 (M - 3PF6)+; 1H NMR(CD3COCD3, 300 MHz, 25 °C) δ 4.15-3.64 (m, 40H), 5.99 (s,8H), 6.81-6.49 (bm, approximately 3H,), 6.99-6.96 (AA′BB′system, 4H, J ) 8 Hz), 7.07-7.04 (AA′BB′ system, 4H, J ) 8Hz), 7.26-7.19 (m, 31H), 8.02 (s, 8H), 8.19-8.17 (d, 8H, J )6 Hz), 9.31-9.29 (d, 8H, J ) 6 Hz); HRMS calcd forC116H114F18N4P3O12 [M - PF6]+ 2189.7359, found 2189.7323(err 1.7).

{[2]-[1,3-Bis{2-(2-(2-[4-[2-(2-(2-(4-tritylphenoxy)-ethoxy)ethoxy)ethoxy]phenoxy]ethoxy)ethoxy)-ethoxy}phenyl][9,18,29,38-tetraazonia[1.1.0.1.1.0]-paracyclophane]rotaxane} Tetrakis(hexafluorophos-phate) (24‚4PF6). A solution of the dumbbell compound 18(0.50 mg, 0.4 mmol), the bipyridinium salt 21‚2PF6 (0.086 g,1.2 mmol), and the dibromide 22 (0.38 g, 1.4 mmol) in dry DMF(10 mL) was stirred for 10 days at room temperature andpressure. Thereafter, Et2O (50 mL) was added to the reactionmixture in order to precipitate all the charged species. Theorange precipitate was filtered and washed with Et2O (50 mL)and CH2Cl2 (50 mL). Column chromatography [SiO2, MeOH:NH4Cl (2 M):MeNO2 (7:2:1)] afforded the rotaxane 24‚4PF6 asa red solid in the form of the chloride salt. The red solid wasdissolved in H2O, and a saturated aqueous solution of NH4PF6

was added dropwise until no further precipitation was ob-served. The red precipitate was filtered off and washedthoroughly with H2O to yield rotaxane 24‚4PF6 as a red powder(0.11 g, 12%) after vacuum drying: mp > 250 °C dec; IR (NaCl)3054, 2921, 1636, 1508, 1452, 1248, 1136, 1056, 842, 702 cm-1;UV/vis λmax (ε) 244 nm (38700), 445 nm (320); LSIMSm/z 2560(M+), 2415 (M - PF6)+, 2270 (M - 2PF6)+, 2125 (M - 3PF6)+;1H NMR (CD3COCD3, 300 MHz, 25 °C) δ 4.07-3.65 (bm,

approximately 52H), 6.00 (s, 8H), 6.82 (bm, approximately 4H),7.02 (bm, approximately 2H), 7.28-7.16 (m, 34H), 8.02 (s, 8H),8.21-8.19 (d, 8H, J ) 6 Hz), 9.34-9.32 (d, 8H, J ) 6 Hz);HRMS calcd for 12C127

13C1H130F18N4O16P3 [M - PF6]+ 2414.8440,found 2414.8352 (err 3.7).

{[2]-[1,4-Bis{2-(2-(2-[3-[2-(2-(2-(4-tritylphenoxy)-ethoxy)ethoxy)ethoxy]phenoxy]ethoxy)ethoxy)-ethoxy}phenyl][9,18,29,38-tetraazonia[1.1.0.1.1.0]-paracyclophane]rotaxane} Tetrakis(hexafluorophos-phate) (25‚4PF6). A solution of the dumbbell compound 20(0.83 g, 0.5 mmol), the bipyridinium salt 21‚2PF6 (1.2 g, 1.7mmol), and the dibromide 22 (0.18 mg, 0.6 mmol) in dry DMF(10 mL) was stirred for 10 days at room temperature andpressure. Thereafter, Et2O (50 mL) was added to the reactionmixture in order to precipitate all the charged species. Theorange precipitate was filtered and washed with Et2O (50 mL)and CH2Cl2 (50 mL). Column chromatography [SiO2, MeOH:NH4Cl (2 M):MeNO2 (7:2:1)] afforded the rotaxane 25‚4PF6 asa red solid in the form of the chloride salt. The red solid wasdissolved in H2O, and a saturated aqueous solution of NH4PF6

was added dropwise until no further precipitation was ob-served. The red precipitate was filtered and washed thor-oughly with H2O to yield the rotaxane 25‚4PF6 as a red powder(0.20 g, 14%) after vacuum drying: mp > 250 °C dec; IR (NaCl)3056, 2922, 2360, 1635, 1507, 1411, 1134, 836, 790, 702 cm-1;UV/vis λmax (ε) 242 nm (38 100), 442 nm (315); LSIMSm/z 2415(M - PF6)+, 2270 (M - 2PF6)+, 2125 (M - 3PF6)+; 1H NMR(CD3COCD3, 300 MHz, 25 °C) δ 4.10-3.64 (m, 52H), 5.99 (s,8H), 6.82 (bs, approximately 6H), 7.07-7.04 (AA′BB′, system,4H, J ) 8 Hz), 7.29-7.15 (m, 34H), 8.02 (s, 8H), 8.24-8.21 (d,8H, J ) 6 Hz), 9.33-9.31 (d, 8H, J ) 6 Hz); HRMS calcd for12C127

13C1H130F18N4O16P3 [M - PF6]+ 2414.8440, found 2414.8486(err -1.9).

Acknowledgment. We thank the Engineering andPhysical Science Research Council for grants to pur-chase mass spectrometry equipment and for a postdoc-toral fellowship (to S.E.B.) and Eusko Jaurlaritza,Unibersitate, Ikerketa eta Hizkuntza Saila, for a pre-doctoral grant (to M.G.-L.).

Supporting Information Available: Copies of NMRspectra (8 pages). This material is contained in libraries onmicrofiche, immediately follows this article in the microfilmversion of the journal, and can be ordered from the ACS; seeany current masthead page for ordering information.

JO9612584


translational isomerism in some two- and three-station [2]rotaxanes†

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